title: Recent advances in understanding and managing adenosine deaminase and purine nucleoside phosphorylase deficiencies.
abstract: OBJECTIVE
  To review the recent advances in the understanding and management of the immune and nonimmune effects of inherited adenosine deaminase (ADA) and purine nucleoside phosphorylase (PNP) deficiencies.
  
  
  RESULTS
  Abnormal thymocyte development and peripheral T-cell activation in ADA-deficient and PNP-deficient patients cause increased susceptibility to infections and immune dysregulation. The impaired purine homeostasis also damages many other cell types and tissues. Animal studies suggest that defects in surfactant metabolism by alveolar macrophages cause the pulmonary alveolar proteinosis commonly seen in ADA-deficient infants, while toxicity of purine metabolites to cerebellar Purkinje cells may lead to the ataxia frequently observed in PNP deficiency. Patients' outcome with current treatments including enzyme replacement and stem cell transplantations are inferior to those achieved in most severe immunodeficiency conditions. New strategies, including intracellular enzyme replacement, gene therapy and innovative protocols for stem cell transplantations hold great promise for improved outcomes in ADA and PNP deficiency. Moreover, newborn screening and early diagnosis will allow prompt application of these novel treatment strategies, further improving survival and reducing morbidity.
  
  
  CONCLUSIONS
  Better understanding of the complex immune and nonimmune effects of ADA and PNP deficiency holds great promise for improved patients' outcome.
authors.affiliation: Division of Immunology and Allergy, Department of Pediatrics, Hospital for Sick Children, University of Toronto, Toronto, Ontario, Canada.
authors.forename: Eyal
authors.initials: E
authors.lastname: Grunebaum
authors.forename: Amos
authors.initials: A
authors.lastname: Cohen
authors.forename: Chaim M
authors.initials: CM
authors.lastname: Roifman
mesh_terms: D000243:Adenosine Deaminase / Q000172:deficiency* / Q000235:genetics / Q000276:immunology / Q000627:therapeutic use; D000361:Agammaglobulinemia / Q000188:drug therapy / Q000201:enzymology / Q000235:genetics / Q000276:immunology / Q000401:mortality; D000818:Animals; D056947:Enzyme Replacement Therapy; D006801:Humans; D008213:Lymphocyte Activation / Q000235:genetics / Q000276:immunology; D016676:Macrophages, Alveolar / Q000201:enzymology / Q000276:immunology; D000081207:Primary Immunodeficiency Diseases; D011683:Purine-Nucleoside Phosphorylase / Q000172:deficiency* / Q000235:genetics / Q000276:immunology / Q000627:therapeutic use; D011686:Purine-Pyrimidine Metabolism, Inborn Errors / Q000178:diet therapy / Q000201:enzymology / Q000235:genetics / Q000276:immunology / Q000401:mortality; D011687:Purines / Q000276:immunology / Q000378:metabolism; D011689:Purkinje Cells / Q000201:enzymology / Q000276:immunology; D016511:Severe Combined Immunodeficiency / Q000188:drug therapy / Q000201:enzymology / Q000235:genetics / Q000276:immunology / Q000401:mortality; D013601:T-Lymphocytes / Q000201:enzymology / Q000276:immunology
chemical_list: D011687:Purines; D011683:Purine-Nucleoside Phosphorylase; C548482:ADA protein, human; D000243:Adenosine Deaminase